Use of Generalized Weighted Quantile Sum Regressions of Tumor Necrosis Factor Alpha and Kidney Function to Explore Joint Effects of Multiple Metals in Blood

Abstract

Exposure to heavy metals could lead to adverse health effects by oxidative reactions or inflammation. Some essential elements are known as reactors of anti-inflammatory enzymes or coenzymes. The relationship between tumor necrosis factor alpha (TNF-α) and heavy metal exposures was reported. However, the interaction between toxic metals and essential elements in the inflammatory response remains unclear. This study aimed to explore the association between arsenic (As), cadmium (Cd), lead (Pb), cobalt (Co), copper (Cu), selenium (Se), and zinc (Zn) in blood and TNF-α as well as kidney function. We enrolled 421 workers and measured the levels of these seven metals/metalloids and TNF-α in blood; kidney function was calculated by CKD-EPI equation. We applied weighted quantile sum (WQS) regression and group WQS regression to assess the effects of metal/metalloid mixtures to TNF-α and kidney function. We also approached the relationship between metals/metalloids and TNF-α by generalized additive models (GAM). The relationship of the exposure–response curve between Pb level and TNF-α in serum was found significantly non-linear after adjusting covariates (p < 0.001). Within the multiple-metal model, Pb, As, and Zn were associated with increased TNF-α levels with effects dedicated to the mixture of 50%, 31%, and 15%, respectively. Grouped WQS revealed that the essential metal group showed a significantly negative association with TNF-α and kidney function. The toxic metal group found significantly positive associations with TNF-α, serum creatinine, and WBC but not for eGFR. These results suggested Pb, As, Zn, Se, and mixtures may act on TNF-α even through interactive mechanisms. Our findings offer insights into what primary components of metal mixtures affect inflammation and kidney function during co-exposure to metals; however, the mechanisms still need further research.

Reversal Effects of Royal Jelly and Propolis Against Cadmium-Induced Hepatorenal Toxicity in Rats

“…TNF-α can activate three diverse pathways: mitogen-activated protein kinase (MAPK), NF-κB, and cell death signaling pathways. The current results agree with the previously reported results [ 46 ]. In this study, RJ and P diminished the inflammatory markers’ elevation, mainly due to their phenolic mixes and other minor constituents [ 47 , 48 ].…”

The mediation effect of Systemic Immunity Inflammation Index between urinary metals and TOFAT among adults in the NHANES dataset

“…Metals are associated with adverse health effects, sarcopenia, osteoporosis, kidney damage, etc [5][6][7]. Previous studies have reported that exposure to As, Cd, cobalt (Co), Pb, and mercury (Hg) could cause chronic diseases such as diabetes and obesity [8][9][10].…”